Osteoarthritis (OA) is the most prevalent joint disease. Almost 4 million people suffer OA, and OA is the cause of 50% total disability in Spain. It affects the quality of life in its physical, emotional and social aspect. The economic impact is such that direct cost of OA in Spain is 4,738 million euros per year. OA is therefore an important problem of Public Health. There is no known cure for OA and its pathogenesis is multifactorial. Besides the bio mechanic factors, trauma and obesity; inflammation plays and important role in knee OA. Several studies and decades of clinical experience state that Ozone acts on the modulation of inflammation. In Chapter 1, the pathophysiology involved in knee OA is reviewed and Ozone is postulated as a promising conservative treatment, since it could act on several targets.In Chapters 2 and 3, Ozone proved to be effective in pain relief, function and quality of life in Knee OA and Chondromalacia. In Chapter 4, Ozone improved minimal joint spacewidth in a two years follow-up Knee OA sample, showing for the first time its disease modifying drug effect for OA (DMDOA). In Chapter 5, the DMDOA effect is confirmed, by presenting a case report.